Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats.
Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats.
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作者：
Oliveira AG;Carvalho BM;Tobar N;Ropelle ER;Pauli JR;Bagarolli RA;Guadagnini D;Carvalheira JB;Saad MJ
饮食诱导的肥胖症（diet-induced obesity，DIO）中的胰岛素抵抗与慢性全身性低度炎症有关，Toll样受体4（Toll like receptor 4，TLR 4）在胰岛素抵抗、炎症和肥胖之间的联系中起重要作用。本研究旨在分析运动对肥胖大鼠TLR 4表达和激活的影响及其对胰岛素敏感性和信号传导的影响。观察慢性和急性运动对DIO大鼠胰岛素敏感性、胰岛素信号转导、TLR 4活化、c-Jun氨基末端激酶（JNK）和IκB激酶β（IKKβ）活性以及血清脂多糖（LPS）水平的影响。结果表明，慢性运动降低了肝脏、肌肉和脂肪组织中TLR 4 mRNA和蛋白的表达。然而，急性和慢性运动都减弱了这些组织中的TLR 4信号传导，包括JNK和IKKβ磷酸化和IRS-1丝氨酸307磷酸化的减少，同时改善了胰岛素诱导的IR，IRS-1酪氨酸磷酸化和Akt丝氨酸磷酸化，并降低了LPS血清水平。我们的研究结果表明，在DIO大鼠，急性和慢性的体育锻炼，诱导在肝脏，肌肉和脂肪组织中的TLR 4信号通路的重要抑制，降低LPS血清水平，并提高胰岛素信号和敏感性。这些数据为我们理解将体育锻炼与炎症和胰岛素抵抗改善联系起来的分子事件提供了相当大的进展。
Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll–like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity. The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling. The effect of chronic and acute exercise was investigated on insulin sensitivity, insulin signaling, TLR4 activation, c-Jun NH2-terminal kinase (JNK) and IκB kinase (IKKβ) activity, and lipopolysaccharide (LPS) serum levels in tissues of DIO rats. The results showed that chronic exercise reduced TLR4 mRNA and protein expression in liver, muscle, and adipose tissue. However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKKβ phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels. Our results show that physical exercise in DIO rats, both acute and chronic, induces an important suppression in the TLR4 signaling pathway in the liver, muscle, and adipose tissue, reduces LPS serum levels, and improves insulin signaling and sensitivity. These data provide considerable progress in our understanding of the molecular events that link physical exercise to an improvement in inflammation and insulin resistance.
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影响因子：
16.2
作者：
Ghanim H;Abuaysheh S;Sia CL;Korzeniewski K;Chaudhuri A;Fernandez-Real JM;Dandona P
通讯作者：
Dandona P
影响因子：
7.7
作者：
Carvalho, MA;Ueno, M;Saad, MJA
通讯作者：
Saad, MJA
影响因子：
2.3
作者：
Matsumura, T;Ito, A;Onozaki, K
通讯作者：
Onozaki, K
影响因子：
8.2
作者：
Monroy, A.;Kamath, S.;Chavez, A. O.;Centonze, V. E.;Veerasamy, M.;Barrentine, A.;Wewer, J. J.;Coletta, D. K.;Jenkinson, C.;Jhingan, R. M.;Smokler, D.;Reyna, S.;Musi, N.;Khokka, R.;Federici, M.;Tripathy, D.;DeFronzo, R. A.;Folli, F.
通讯作者：
Folli, F.
影响因子：
4.4
作者：
Faure, E;Thomas, L;Arditi, M
通讯作者：
Arditi, M